Phase I and Pharmacokinetic Study of Fostriecin given as an Intravenous Bolus Daily for Five Consecutive Days

Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. A phase I study was conducted to evaluate the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of this drug. Forty-six patients were treated with escalating doses of fostriecin (2-47 mg/m2) administered as a daily bolus infusion for five consecutive days. PK studies were performed at different time points following administration of fostriecin. Dose-limiting toxicities included: elevation of creatinine, bilirubin, and hepatic transaminases; nausea, anorexia, lethargy, and hypotension. PK studies were compatible with a two-compartment model. Regression analysis revealed a significant relationship between dose and clearance; however, the r2 value was only 0.168 indicating a low predictive value for the model. No significant difference was seen in PK parameters with repeated dosing during the same cycle. Although no tumor responses were seen, 16 patients had stable disease with a median duration response of 2.6 months. The study was closed before reaching MTD due to problems with the supply of fostriecin from the National Cancer Institute of the United States (NCI US). New methods for synthesizing fostriecin have recently been described and therefore further development of this unique anticancer agent may be warranted.     

Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial

BACKGROUND: The purpose of this study was to compare gastrointestinal tolerance to two enteral feeding protocols in critically ill patients. METHODS: A prospective, randomized controlled trial, that involved 96 consecutive patients expected to stay in the intensive care unit for > or =3 days and who had no contraindications to enteral feeding. The patients were randomized to either the current protocol (group I; gastric residual volume threshold, 150 mL, optional prokinetic) or proposed feeding protocol (group II; gastric residual volume threshold 250 mL, mandatory prokinetic). Gastrointestinal intolerance was recorded as episodes of high gastric residual volume, emesis, or diarrhea. The time to reach the goal rate of feeding and the percentage of nutritional requirements received during the study period were also recorded. RESULTS: Nineteen of 36 patients (19/36 = 0.53) in group I had one or more episodes of high gastric residual volume, compared with 10 of 44 patients (10/44 = 0.23) in group II (p < .005). There was no statistical difference between the two protocols with regards to emesis, diarrhea, or the total episodes of intolerance. The patients in group II reached their goal rates on average in 15 hours and received 76% of their nutritional requirements, compared with 22 hours and 70% in group I; however, these differences were not statistically significant. CONCLUSIONS: The incidence of enteral feeding intolerance was reduced by using a gastric residual volume of 250 mL along with the mandatory use of prokinetics. The study showed a trend of improved enteral nutrition provision and reduced the time to reach the goal rate in group II. These improvements support the adoption of the proposed feeding protocol for critically ill patients.     

甲硝唑葡萄糖注射液细菌内毒素检查法的研究

目的;以细菌内毒素检查法对甲硝唑葡萄糖注射液进行试验研究。方法;采用抑制或增强试验,并将细菌内毒素检查法与家兔法检测结果作对比。结果：该注射液经一定稀释后对测定无干扰。结论：细菌内毒素检查法适用于检测该注射液。     

Ocular MR imaging and spectroscopy: an ex vivo study

Six eyes, freshly enucleated because of choroidal melanoma, were imaged on a 1.4-T superconducting magnetic resonance (MR) imaging system, and relaxation times were calculated for various parts of the eye. Unfixed fresh tissue samples were obtained for nuclear magnetic resonance spectroscopy (NMRS) on a variable-field (0.19-1.4 T) resistive unit. Detailed ocular anatomy was demonstrated. The NMRS relaxation times correlated with the MR imaging intensity patterns. The sensitivity of MR imaging to states of hydration provides an excellent window for appreciation of ocular anatomy.     

Athlete shoulder injuries: CT arthrographic findings

Forty-three professional and amateur athletes with persistent shoulder pain that interfered with their sports activities were evaluated by computed tomographic (CT) arthrography. In 19 patients, glenohumeral instability (14 anterior, two posterior, three multidirectional) was diagnosed with CT arthrography based on the simultaneous presence of labral and capsular lesions. The findings were crucial in establishing the diagnosis of instability in six patients in whom the condition was not suggested or could not be confirmed clinically. Another significant injury consisted of labral lesions not associated with glenohumeral instability. These tears often involved the anterior and parasuperior segments of this structure. Other, less frequently detected lesions included segmental labral enlargement and several labra with abnormal orientation (everted labrum). Early onset of degenerative disease was present in many athletes, especially those with a long history of sports activity. CT arthrographic findings were correlated with arthroscopic or surgical results in 19 patients.     

No evidence of frequent human immunodeficiency virus type 1 infection in seronegative at-risk individuals

The possible existence of human immunodeficiency virus type 1 (HIV-1) infection in asymptomatic seronegative at-risk individuals was investigated in a prospective study of 55 seronegative high-risk individuals (42 homosexual men and 13 heterosexual individuals) and 32 seronegative hemophiliacs treated with factor VIII or IX concentrates before viral inactivation by heat treatment and systematic screening of blood donations. Tests used include the polymerase chain reaction assay with three primer pairs (one in the gag region and two in the pol region) and tests for serum p24 antigen, anti-nef serology (Western blot), and five biologic markers frequently altered by HIV infection (CD4 lymphocyte count, serum beta 2-microglobulin and neopterin concentration, and serum IgG and IgA concentration). Although 91 of 92 HIV-1-seropositive persons were positive in testing with at least one primer pair, no positive result was observed in seronegative at-risk individuals or in 117 seronegative low-risk controls. No nef antibody was found in seronegative at-risk individuals or seronegative controls, but 44 (47%) of 92 HIV-1-seropositive persons had nef antibodies. These findings do not support the existence of frequent HIV-1 infection in seronegative at-risk individuals.